Improving the clinical outcomes of total hip replacement continues to be limited by our understanding of the damage response of the system that causes loosening and the multi-factorial nature of the loosening process. Retrospective clinical data point to design, patient, and surgical factors that have an effect on the loosening process, but are often unable to underscore the failure mechanism. Implant migration in the short-term is a strong predictor of clinical loosening suggesting that there are negative factors built in at the time of surgery that contribute to eventual failure. During this last grant cycle, in vitro prepared cemented stem constructs have proven useful to elucidate some relationships between construct morphology and loosening process, but these experiments were limited to lab-prepared specimens and focused on interfacial failure mechanisms. The long-term goal of this research program is to achieve arthroplasties that function successfully for the lifetime of the patient without need for revision. Towards this end, we propose to develop robust experimental and computational tools that can be used for pre-clinical assessment of cemented total hip replacements after initial implantation. The approach used here is to (1) determine the fatigue damage/loosening response of components of the cemented hip construct, (2) combine these to assess the relative contribution to the overall evolution of the fatigue damage/loosening process, (3) validate that the mechanical response of in vitro prepared structures are comparable to post-mortem retrieved structures and (4) assess the role of clinically relevant surgical procedures on the loosening process. Construct morphology is carefully quantified or controlled as this is suspected as having an important role in mechanical function. In summary, we are addressing the long-term goal of improving outcomes of cemented hip replacements from three complementary levels: understanding the fundamental mechanics of individual components of the implant system using both in vitro prepared and post-mortem retrievals, developing a comprehensive damage model that can be used to assess the short-term outcome of implant systems, and assessing the response of clinically relevant variables. This work will be directly applicable to improving public health through development of pre-clinical tests to assess implant components and surgical techniques and to determine conditions that reduce the risk of loosening of joint replacements.